Benzyl 1,3-Butadiene-1-carbamate

(1; R = Ph)

[65899-49-2]  · C12H13NO2  · Benzyl 1,3-Butadiene-1-carbamate  · (MW 203.09) (2; R = Me)

[61759-61-3]  · C7H11NO2  · Ethyl 1,3-Butadiene-1-carbamate  · (MW 141.08)

(1,3-dienes: useful aminobutadiene equivalents for Diels-Alder reaction,1 regio- and stereoselective reactions even with poor dienophiles;2 used in the synthesis of complex heterocyclic natural products3 and aminoanthraquinones4)

Physical Data: 5-7 (1) mp 74-75 °C; 1H NMR (CDCl3) d 7.32 (s, Ph), 6.71 (br d, J = 9 Hz, =CHNH), 6.26 (dt, J = 10, 17 Hz, CH=CH2), 5.4-5.8 (m, CH=CHNH and NH), 5.15 (s, CH2Ph), 4.8-5.2 (m, =CH2); 13C NMR (CDCl3) d 127.2, 112.5, 134.6, 113.5, 128.3, 128.4, 128.7, 136.0, 153.7, 67.5. (2) mp 44-45 °C; 1H NMR (CDCl3) d 7.7 (br d, NH), 5.3-6.9 (m, vinylic), 4.5-5.1 (m, =CH2), 4.13 (q, J = 7 Hz, Me); 13C NMR (CDCl3) d 127.6, 112.1, 134.8, 113.2, 14.5, 61.7, 154.1.2,5

Solubility: (1) readily sol dioxane and toluene; (2) sol dioxane.

Preparative Methods: The synthesis of various N-acyl-1-amino-1,3-dienes have been described in detail.6-10 The following, which uses a Curtius rearrangement (eq 1),7 illustrates the procedure commonly used in the synthesis of (1) and (2).

Handling, Storage, and Precautions: in general, acyl azides are potentially explosive. Therefore solutions containing acyl azides should not be evaporated to dryness.5 Both (1) and (2) are stable solids, which can be stored in a freezer for several months. However, they are acid-sensitive and may be decomposed by traces of deuterium chloride present in chloroform-d.5 In rigorously degassed (oxygen-free) solutions, these diene carbamates are stable for extended periods even at 140 °C and this has been a critical factor in their successful reactivity with poor dienophiles.2

Diels-Alder Reactions.

Both (1) and (2) react with a broad range of dienophiles, providing a variety of amino-functionalized cycloadducts in high yields. Reaction with methyl acrylate yields cyclohexenes with high regio- and stereoselectivity (endo) (eq 2).6 In contrast, with the same dienophile, 2,4-pentanedienoic acid requires longer reaction times and gives a mixture of all the possible stereo- and regioisomers.1

The ability to give endo selectivity, coupled with their higher reactivity, is, in part, responsible for the versatility of (1) and (2) in natural product synthesis. The construction of three of the chiral centers found in (±)-pumiliotoxin C was achieved in a single step (eq 3).11,12 While other dienes exhibited lower stereoselectivities with trans-crotonaldehyde,13,14 (1) and (2) gave the endo products in 61 and 67% yields, respectively; these were key intermediates in the synthesis of (±)-pumiliotoxin C.12 Additionally, use of a chiral dienophile, (5R)-5-hydroxy-6,6-dimethylhept-2-en-4-one, permitted the asymmetric synthesis of (+)-pumiliotoxin C.15

The cycloaddition of benzyl trans-1,3-butadiene-1-carbamate (1) and ethyl atropate affords the major product endo; this was a key intermediate in the synthesis of (±)-tilidine (eq 4).16 Of significance is the opposite stereoselectivity exhibited by the related trans-1-(dialkylamino)-1,3-dienes (R1 = R2 = Me).17,18

The most remarkable feature of dienes (1) and (2) is their ability to give endo cycloaddition products, in good yields, with extremely poor dienophiles such as methyl trans-crotonate, trans-crotonaldehyde, 2-cyclohexenone, styrene, and 3,4-methylenedioxystyrene.2,11,19-24 The reaction of (1) with phenylacetylene (140 °C, 114 h),2 however, led to a mixture of 13 products, suggesting an upper limit to the reactivity of these dienes.

To date, Diels-Alder reactions involving (1) and (2) have been the key step in syntheses of gephyrotoxin,26 (±)-perhydrogephyrotoxin,25 (+)-pumiliotoxin,11,15 (±)-isogabaculine,27 and (±)-tilidine.16 In addition, substituted aminoanthraquinones have been synthesized by the regioselective cycloaddition of (1) to naphthoquinones followed by aromatization.4,28 Also noteworthy is the synthesis of epimeric cis-decahydroquinoline-5-carboxylic acids, which involved the reaction of (1) with trans-3-acetylcrotonaldehyde.29 Additionally, the presence of an easily modifiable phenyl group in (1) has led to the generation of a water-soluble diene (eq 5), which has been used in antibody-catalyzed Diels-Alder reactions.30 Exclusive formation of either isomer (endo or exo) has been possible, depending on the transition state analog used for the elicitation of catalytic antibodies.30


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28. Chigr, M.; Fillion, H.; Rougny, A.; Berlion, M.; Riondel, J.; Beriel, H. CPB 1990, 38, 688.
29. Witiak, D. T.; Tomita, K.; Patch, R. J.; Enna, S. J. JMC 1981, 24, 788.
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Dev P. Arya & David J. Jebaratnam

Northeastern University, Boston, MA, USA



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